Cancer is the second leading cause of death in the United States. In 2001, nearly 1.3 million Americans were diagnosed with cancer. The goal of this proposal is to establish the pre-clinical relevancy of a proprietary reversible linker, A-Z-CINN/TM, in creating a novel class of targeted pro-drugs (TARPs) as a single treatment cure for cancer. A-Z-CINN TARPs are modular constructs, which combine the targeting capabilities of monoclonal antibodies with the killing effectiveness of chemotherapy drugs. If the research is successful, A-Z-CINN TARPs will become a revolutionary anti-cancer therapy: conjugates that yield targeted destruction of tumor cells in a single treatment. This will lead to creation of a library of A-Z-CINN TARPs for treatment of primary and metastatic tumors. Specific aims of our research are: 1) Establish A-Z-CINN Linker as a viable platform technology for targeted anti-cancer drug delivery in vitro; 2) Create an initial library of five A-Z-CINN TARP conjugates in preparation for pre-clinical animal studies, and 3) Establish pre-clinical efficacy of TARPs in destroying tumors in a single treatment. Following successful completion of this research, AuraZyme will initiate pre- clinical safety and toxicology studies in support of an investigational New Drug Application with the FDA. PROPOSED COMMERCIAL APPLICATIONS: A-Z-CINN TARPS will become a platform technology for anti-cancer treatments. We will enter joint development and marketed partnerships with biotech and pharmaceutical companies. For Biotech companies A- Z-CINN will enhance the therapeutic benefit of their chemotherapy drugs.